Curcumin (diferuloylmethane or (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is contained in turmeric (Curcuma longa L.), which is a yellow pigment used as a spice. Curcumin exerts inhibitory activity in the growth of various cancer cells, including, e.g., colon cancer, breast cancer, and prostate cancer. Curcumin is well-known from investigations in mouse models to be active in preventing carcinogenesis and inhibiting the occurrence of adenomas, which are precancerous lesions of colon cancer.
The activity in inhibiting the growth of cancer cells, the anti-carcinogenic activity, and other pharmacological activities of curcumin are described in, e.g., Non-Patent Documents 1, 2, 3. Non-Patent Document 1 describes the effect of curcumin in inhibiting the growth of colon cancer cells at a concentration of 20 μM and in degrading β-catenin at a concentration of 15 μM. However, the water-solubility of curcumin is poor, and improving the activity of inhibiting cell growth is difficult.
Curcumin-like compounds such as 1,5-bis(3,4-dimethoxyphenyl)-1,4-pentadien-3-one (BDMPP) that have improved water-solubility and enhanced activity are described in Non-Patent Document 2, but the compounds BDMMMPP and BBMMPP synthesized in the present invention are not described therein, and BTMP is also not described. A description of the anti-carcinogenic activity of BDMPP is also not present.
Non-Patent Document 3 describes a decrease of approximately 40% in the occurrence of adenomas, which are precancerous lesions, after oral administration of curcumin having β-catenin-degrading activity in a mouse strain having a high incidence of colon cancer, but there is no description of the synthesis of the compound having strong β-catenin-degrading activity. A method for synthesizing BTMP is described in Non-Patent Document 4, but this document does not contain a description of the anti-cancer effect thereof.
Non-Patent Document 1: Jaiswal A. S. et al., Oncogene, 21, pp. 8414-8427 “β-Catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells,” 2002.
Non-Patent Document 2: Adams B. K. et al., Bioorganic & Medicinal Chemistry, 12, pp. 3871-3883 “Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents,” 2004.
Non-Patent Document 3: Perkins S. et al., Cancer Epidemiology, Biomarkers & Prevention, 11, pp. 535-540 “Chemopreventive efficacy and pharmacokinetics of curcumin in the Min/+mouse, a model of familial adenomatous polyposis,” 2002.
Non-Patent Document 4: Esther Caballero et al., Tetrahedron, 54, pp. 6111-6122 “Synthesis of (±)-7-(3,4,5-trimethoxyphenyl)-7-deoxyidarubicinone. A new family of anthracycline analogues,” 1998.